Radioligand therapy (RLT) used to treat cardiac metastasis of pancreatic neuroendocrine tumor.

Radioligand Therapy (RLT) in the form of [177Lu] Lu-DOTA-TATE (Lutathera®) is a promising treatment for pancreatic neuroendocrine tumors (pNETs) with cardiac metastasis. We present a patient treated with [177Lu] Lu-DOTA-TATE that showed shrinkage of metastasis after four treatments at 7.4 GBq every 8 weeks.

Potential for Nuclear Medicine Therapy for Glioblastoma Treatment.

Glioblastoma is the most common malignant adult brain tumor and has a very poor patient prognosis. The mean survival for highly proliferative glioblastoma is only 10 to 14 months despite an aggressive current therapeutic approach known as Stupp's protocol, which consists of debulking surgery followed by radiotherapy and chemotherapy. Despite several clinical trials using anti-angiogenic targeted therapies, glioblastoma medical care remains without major progress in the last decade. Recent progress in nuclear medicine, has been mainly driven by advances in biotechnologies such as radioimmunotherapy, radiopeptide therapy, and radionanoparticles, and these bring a new promising arsenal for glioblastoma therapy. For therapeutic purposes, nuclear medicine practitioners classically use ß- particle emitters like 131I, 90Y, 186/188Re, or 177Lu. In the glioblastoma field, these radioisotopes are coupled with nanoparticles, monoclonal antibodies, or peptides. These radiopharmaceutical compounds have resulted in a stabilization and/or improvement of the neurological status with only transient side effects. In nuclear medicine, the glioblastoma-localized and targeted internal radiotherapy proof-of-concept stage has been successfully demonstrated using ß- emitting isotopes. Similarly, α particle emitters like 213Bi, 211At, or 225Ac appear to be an innovative and interesting alternative. Indeed, α particles deliver a high proportion of their energy inside or at close proximity to the targeted cells (within a few micrometers from the emission point versus several millimeters for ß- particles). This physical property is based on particle-matter interaction differences and results in α particles being highly efficient in killing tumor cells with minimal irradiation of healthy tissues and permits targeting of isolated tumor cells. The first clinical trials confirmed this idea and showed good therapeutic efficacy and less side effects, thus opening a new and promising era for glioblastoma medical care using α therapy. The objective of this literature review is focused on the developing field of nuclear medicine and aims to describe the various parameters such as targets, vectors, isotopes, or injection route (systemic and local) in relation to the clinical and preclinical results in glioblastoma pathology.

Management of functional neuroendocrine tumors of the pancreas.

Pancreatic neuroendocrine tumors (pNETs) constitute a heterogenous group of malignancies with varying clinical presentation, tumor biology and prognosis. The incidence of pNETs has steadily increased during the last decades with an estimated incidence 2012 of 4.8/100,000. Recent whole genome sequencing of pNETs has demonstrated mutations in the DNA repair genes MUTYH and point mutations and gene fusions in four main pathways from chromatin remodeling, DNA damage repair, activation of mechanistic target of rapamycin (mTOR) signaling and the telomere maintenance. This new information will be the foundation for new therapies in the near future for malignant pNETs. The functioning pNETs constitute about 30-40% of all pNETs displaying nine different clinical syndromes: insulinoma, Zollinger-Ellison, Verner-Morrison, glucagonoma, somatostatinomas, ectopic adrenocorticotropic hormone (ACTH) and parathyroid hormone related peptide (PTH-rP) syndromes. Single patients might also present carcinoid syndrome. The diagnostic work-up include histopathology with the new WHO 2017 Classification, biomarkers (CgA, NSE), radiology and molecular imaging including CT-scan, magnetic resonance imaging (MRI), ultrasound and PET-scan. A cornerstone in the treatment of pNETs is surgery which is rarely curative but can reduce the clinical symptoms by debulking which also include radiofrequency ablation, embolization of liver metastases. Medical treatment includes chemotherapy and the targeted agents such as everolimus, sunitinib and peptide receptor radiotherapy (PRRT). Somatostatin analogs has for the last decades been the main stay for management for clinical symptoms related to functioning pNETs and is often combined with new targeted agents as well as chemotherapy. Long-term management of functioning pNETs need a combination of different procedures, surgery, local ablation, targeted agents and somatostatin analogs. Future therapies might be based on the recent advances in molecular genetics and tumor biology.

(68)Ga-DotaTATE PET-CT followed by Peptide Receptor Radiotherapy in combination with capecitabine in two patients with Merkel Cell Carcinoma.

Herein, we report about two Caucasian patients with the histopathological diagnosis of Merkel cell carcinoma suffering from extensive lymph node metastases. The extent of the disease was diagnosed by Ga-68-DotaTATE-PET-CT. Both patients had rapid disease progression, one of them despite a three months course of sunitinibe followed by four chemotherapy cycles of cisplatin and etoposide. Both patients were sent for peptide receptor radiotherapy with 90Y-DotaTATE or 177Lu-DotaTATE in combination with capecitabine. Additional external beam radiotherapy of the cervical and inguinal lymph nodes was given to the patient with progressive disease despite chemotherapy. Temporary partial response in both patients was achieved. Despite extensive therapeutic efforts, fatal outcome could not be prevented 10 and 14 months after first clinical symptoms.